Growth Differentiation Factor-15 Is a Novel Biomarker Predicting Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Mutlu, Levent Cem; Altıntaş, Nejat; Aydın, Murat; Tülübaş, Feti; Oran, Mustafa; Kucukyalin, Volkan; Kaplan, Gizem; Gürel, Ahmet

doi:10.1007/s10753-015-0158-5

Cited by 27 publications

(25 citation statements)

References 33 publications

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“…Fourth, there is a lack of longitudinal follow-up for some of the patients, especially among patients with an apparently poor prognosis at inclusion and also with a high mortality, thus our findings in this patient category may be less robust (see supplementary material for details). Finally, although increased systemic levels of GDF15 are associated with both COPD [21] and lung injury [11], GDF15 is not lung specific, and we cannot tell whether the source of GDF15 is from lung tissue or other organ systems.…”

Section: Discussionmentioning

confidence: 95%

“…As a cytokine associated with both inflammation and cachexia, along with increased mortality, GDF15 is of interest in patients with COPD, both as a diagnostic or prognostic biomarker and as a potential treatment target. A few smaller studies have examined GDF15 in COPD, indicating elevated plasma levels of GDF15 in patients with COPD [21,22], and an additional increase during COPD exacerbations [21,23,24]. Nevertheless, the role of GDF15 as a prognostic biomarker in COPD is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD

et al. 2017

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Increased levels of growth differentiation factor-15 (GDF15) are associated with cachexia, cardiovascular disease and all-cause mortality. The role of GDF15 in chronic obstructive pulmonary disease (COPD) is unknown.The study included 413 patients with COPD from the Bergen COPD Cohort Study. All patients had a forced expiratory volume in 1 s (FEV) <80% predicted, a FEV to forced vital capacity (FVC) ratio <0.7 and a history of smoking. Spirometry, fat free mass index, blood gases and plasma GDF15 were measured at baseline. Patients were followed for 3 years regarding exacerbations and changes in lung function, and 9 years for mortality. Yearly exacerbation rate, survival and yearly change in FEV/FVC were evaluated with regression models.Median plasma GDF15 was 0.86 ng·mL (interquartile range 0.64-1.12 ng·mL). The distribution was not normal and GDF15 was analysed as a categorical variable. High levels of GDF15 were associated with a higher exacerbation rate (incidence rate ratio 1.39, 95% CI 1.1-1.74, p=0.006, adjusted values). Furthermore, high levels of GDF15 were associated with higher mortality (hazard ratio 2.07, 95% CI 1.4-3.1, p<0.001) and an increased decline in both FEV (4.29% 3.25%) and FVC (2.63% 1.44%) in comparison to low levels (p<0.01 for both).In patients with COPD, high levels of GDF15 were independently associated with a higher yearly rate of exacerbations, higher mortality and increased decline in both FEV and FVC.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD

et al. 2017

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“…Until now, only circulating GDF-15 levels were reported to be increased in stable COPD and during acute exacerbations of COPD and identified to be an independent predictor of acute exacerbations. [17][18][19] Equivalently, GDF-15 is augmented in serum and lung tissue of patients with pulmonary arterial hypertension. 20,21 Lambrecht et al 22 showed that serum GDF-15 levels correlate with the extent of lung fibrosis in patients with systemic sclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…16 Recently, increased serum levels of GDF-15 have been shown in patients with COPD under stable conditions and during acute exacerbations. [17][18][19] In this study, we explored the potential role of GDF-15 in CS-induced inflammation and COPD. We first analyzed the expression of GDF-15 in the airways and lungs of patients with COPD, in CS-exposed cultures of primary human bronchial epithelial cell cultures (pHBECs) and in lungs of CS-exposed mice.…”

Section: Introductionmentioning

confidence: 99%

Elevated GDF-15 contributes to pulmonary inflammation upon cigarette smoke exposure

et al. 2017

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The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-β superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-β superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice. Next, we exposed GDF-15 KO and control mice to air or CS and evaluated pulmonary inflammation. GDF-15 levels were higher in sputum supernatant and lung tissue of patients with COPD and smokers without COPD compared with never smokers. Immunohistochemistry revealed GDF-15 staining in the airway epithelium. Increased expression and secretion of GDF-15 was confirmed in vitro in CS-exposed pHBECs compared with air-exposed pHBECs. Similarly, GDF-15 levels were increased in lungs of CS-exposed mice. Importantly, GDF-15 deficiency attenuated the CS-induced pulmonary inflammation. These results suggest that increased GDF-15-as observed in lungs of smokers and patients with COPD-contributes to CS-induced pulmonary inflammation.

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“…It is suggested to have an overall anti-inflammatory effect and is elevated in inflammatory scenarios associated with cancer, cardiovascular disease, insulin resistance and obesity 25 , as a compensatory mechanism 26 – 28 . GDF15 levels have been reported to correlate with CRP levels in certain inflammatory disorders 29 , 30 . In addition to its growing relevance as a marker of inflammation 26 and all-cause mortality 31 , GDF15 has been described in the literature to have neurotrophic 32 , 33 and anti-apoptotic properties 34 .…”

Section: Introductionmentioning

confidence: 99%

Plasma GDF15 level is elevated in psychosis and inversely correlated with severity

Kumar

Millischer

Villaescusa

et al. 2017

Sci Rep

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Accumulating evidence suggests that GDF15 is a biomarker for ageing and morbidity of many somatic disorders such as cancer and inflammatory disorders. Recently, elevated serum GDF15 level was proposed as a marker for mood disorder. However, psychosis severity was not investigated in relation to plasma GDF15 levels. In the present study we measured GDF15 levels in plasma of 120 psychosis patients compared to 120 age and gender matched healthy controls. Within the patient cohort GDF15 levels were evaluated for association with age, gender, lifestyle factors, C-reactive protein levels, psychosis severity and metabolic disorder. Psychosis patients had elevated GDF15 levels compared to controls (medianPsychosis = 744 ng/mL, mediancontrols = 516 ng/mL, p < 0.001). Within the psychosis cohort, GDF15 levels, when corrected for age, metabolic health and lifestyle factors, were negatively correlated with psychosis severity (β = −0.218, p = 0.012). While GDF15 levels were elevated in patients versus healthy controls, the negative correlation between psychosis severity and GDF15 suggests a loss of anti-inflammatory GDF15 mediated functionality in severe psychosis. Study replication in larger cohorts will be necessary to assess the potential of GDF15 as a prognostic biomarker in psychosis.

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Growth Differentiation Factor-15 Is a Novel Biomarker Predicting Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Cited by 27 publications

References 33 publications

Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD

Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD

Elevated GDF-15 contributes to pulmonary inflammation upon cigarette smoke exposure

Plasma GDF15 level is elevated in psychosis and inversely correlated with severity

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